MODULATION OF HYPERTENSIVE HEART-DISEASE BY ESTROGEN

Left ventricular hypertrophy is an independent risk factor for morbidi ty in patients with hypertensive heart disease. Cardiac hypertrophy, a ssociated with increased cardiac fibrosis and myocardial relaxation im pairment, shows gender-based differences with significantly higher mor tality in men. The role of estrogen in the pathogenesis of this proces s is poorly understood. After our previous demonstration that cardiac myocytes and fibroblasts contain functional estrogen receptors, we the refore investigated: 1) the influence of different estrogen metabolite s on cardiac fibroblast growth; 2) the influence of different estrogen metabolites on the expression of the immediate early gene c-Fos; 3) t he influence of estrogen on the L-type calcium channel in cardiomyocyt es. Methods: 1) Neonatal rat cardiac fibroblasts were incubated with 1 7 beta-estradiol, estrone, 2-hydroxyestrone, and 2-methoxyestradiol (a ll 10(-9) M). Bromodeoxyuridine incorporation was measured after 24 h. 2) c-Fos expression was demonstrated by immunoblotting. 3) L-type (Ca 2+) current with and without 17 beta-estradiol was assessed in adult g uinea pig cardiomyocytes by whole cell patch clamp. Results: Cardiac f ibroblast growth was stimulated by estrogen metabolites with 2-hydroxy estrone as the most potent activator; in addition, 10(-5) M 17 beta-es tradiol reduced the L-type Ca2+ current by about 20% in cardiomyocytes . Conclusions: Estrogen induces both short term effects (non-genomic) and long term effects (genomic) on the heart and may therefore account for gender- and age-based differences in hypertensive heart disease.